When a metal combines with an electron donor ligand, a complex or coordination compound is formed. Further, when an electron donor contains two or more donor groups tied together in some way, the ligand is referred to as a polydentate ligand, e.g., a bidentate ligand has two donor groups. The commonality found in all chelates is the formation of a heterocyclic ring comprised of a ligand and a metal atom. For ring formation to occur, several conditions must be present. First, the electron donor molecule must contain two or more groups that can each combine with a particular metal atom. Second, groups and/or atoms must be present that can simultaneously coordinate with the metal atom through their electron pairs. Finally, these donor groups must be separated from each other by sufficient atoms so that sterically permissible heterocyclic rings may be formed. An example of a chelate involving two organic ligands, each ligand containing a carboxyl functional group and an .alpha.-amine functional group, may be depicted by the following graphic: ##STR1## In the above depiction, M represents the metal atom that acts as the closing member for the organic ligands.
The structure, chemistry and bioavailability of amino acid chelates are well documented, e.g. Ashmead et al., Chelated Mineral Nutrition, (1982), Chas. C. Thomas Publishers, Springfield, Ill.; Ashmead et al., Intestinal Absorption of Metal Ions, (1985), Chas. C. Thomas Publishers, Springfield, Illinois; Ashmead et al., Foliar Feeding of Plants with Amino Acid Chelates, (1986), Noyes Publications, Park Ridge, N.J.; U.S. Pat. Nos. 4,020,158; 4,167,564; 4,216,143; 4,216,144; 4,599,152; 4,774,089; 4,830,716; 4,863,898 among others.
Additionally, flavored effervescent mixtures of vitamins and amino acid chelates in the form of a beverage have also been disclosed in U.S. Pat. No. 4,725,427.
In the field of mineral nutrition, amino acid chelates have increasingly been recognized as providing certain advantages over inorganic mineral salts. One advantage is attributed to the fact that these chelates are readily absorbed in the intestines via mucosal cells by means of active transport as though they were small peptides. In other words, the minerals are absorbed along with the amino acids as a single unit by utilizing the amino acids as carrier molecules. This method of metal absorption is beneficial because it enables absorption of specific metals into the body without utilizing standard absorption sites for free metal ions. Therefore, the problems associated with the competition of ions for active sites and the suppression of specific nutritive mineral elements by others are avoided. Other advantages of amino acid chelates include stimulation of gonadotropic hormones as is disclosed in U.S. Pat. No. 4,774,089, delivery of metal ions to targeted tissue sites disclosed in U.S. Pat. No. 4,863,898 and enhancement of the immune system disclosed in U.S. Pat. No. 5,162,369.
Creatine, also known as N-(Aminoiminomethyl)-N-methylglycine, methylglycoamine or N-methyl-guanido acetic acid is a well known substance. In fact, creatine is listed in The Merck Index, Twelfth Edition, No. 2637, and may be represented as follows: ##STR2## It is important to note that creatine is susceptible to cyclization. Perhaps, because of the positioning of the NH.sub.2 gamma to the carboxylic acid, creatine is labile to acid hydrolysis. Regardless of any purported rational, under acidic conditions, creatine has the propensity to form creatinine, which may be represented by the following formula: ##STR3## In fact, in acidic aqueous solutions, the formation of creatinine from creatine is nearly quantitative and irreversible. Cannan, Shore, Biochem. J. 22, 924 (1928). With this in mind, it is apparent that the exposure of creatine to the acidic environment of the stomach will cause an irreversible formation of creatinine. Once creatinine is formed, any further biological use of ingested creatine will be precluded.
Muscle contraction and relaxation are fueled by energy liberated during the dephosphorylation of adenosinetriphosphate (ATP). The ATP stored within a cell is rapidly depleted during even normal activity. For normal tissue function to continue, ATP must be rapidly resynthesized from its breakdown products, one of which is adenosinediphosphate (ADP). During maximal exercise of a short duration, this resynthesis is accomplished almost exclusively by the anaerobic degradation of phosphocreatine (PCR) and glycogen. Hultman E. et al., Energy metabolism and fatigue; Taylor A. et al., eds. Biochemistry of exercise VII, Champaign, Ill., Human Kinetic Publishers, 1990: vol. 21, 73-92. It has also been proposed that the observed decline in force production during intense muscle contraction may be related to the availability of muscle PCR stores. Greenhaff P. L. et al., Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man, Clinical Science (1993) 84, 565-571. The depletion of these PCR stores limits the rephosphorylation of ADP, thereby limiting the ATP available for energy production. Greenhaff further proposed that any mechanism capable of increasing the total intramuscular creatine store might arrest PCR depletion during intense muscular contraction and offset, or even prevent, the decline in the rate of ADP rephosphorylation during exercise. However, no efforts were made to explain the increase of creatine within the muscle cells. Greenhaff merely relied upon work previously published that demonstrated that the creatine content of skeletal muscles could be increased by 20%-50% through standard oral pathways. However, in that study, in order to achieve this marginal increase in the creatine content of muscle cells, the subjects of the study were required to ingest 20 grams of creatine hydrochloride. Harris R. C. et al., Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation, Clin. Sci., 1992; 83: 367-74.
Creatine can be found biologically in diverse portions of the body. However, some reports indicate that creatine is found primarily in the nerves and muscle. Walker J. B., Creatine: Biosynthesis, regulation, and function; Adv. Enzymology and Related Areas of Molecular Biology (1979) 50: 177-242. Essentially, creatine is used biologically for the regeneration of ATP from ADP. However, in the process of regenerating ATP, creatine is irreversibly transformed to creatinine which in turn, is eliminated from the body through the urine. Because creatine is irreversibly used, i.e., from creatine to creatinine, the body must either produce creatine biochemically or secure an outside source to supply the body with needed creatine.
Biochemically, the human liver and pancreas use various amino acids such as glycine, serine, arginine and methionine to synthesize creatine. However, when sufficient in one's diet, creatine may be made bioavailable through ingestion. Although animal muscle contains approximately 0.5% creatine by weight, most of the creatine which is bioavailable for ingestion is degraded by the cooking process. Therefore, cooked meat is a poor source of ingestible creatine. Moreover, plants and/or vegetables are also a poor source of creatine.
The securing of creatine from an outside source has also been discussed in several recent U.S. patents. U.S. Pat. No. 5,397,786 entitled, REHYDRATION DRINK, discloses a drink for the treatment and prevention of the loss of essential electrolytes due to fluid loss. This patent teaches that creatine, B vitamins, pantothenic acid and choline are energy enhancers. Additionally, this invention provides for the addition of numerous salts such as MgCO.sub.3, CaCO.sub.3 and magnesium aspartate as supplements containing essential nutrients. Although the necessity of these elements in a healthy metabolism was recognized, the use of ionic salts is largely ineffective because most of the ingested elements are lost in the acidic environment of the stomach.
U.S. Pat. No. 5,576,316 entitled METHOD FOR INHIBITING TUMOR GROWTH RATE USING CREATINE OR CREATINE ANALOGS discloses the use of creatine and creatine analogs for the treatment of tumors. Specifically, this invention teaches that the administration of creatine in the form of a salt can reduce a tumor's growth rate. The patent further teaches that significant portions of orally administered creatine are lost through the urine without having been used by the body at all.
Finally, U.S. Pat. No. 5,888,553 entitled NON-STEROIDAL ANABOLIC COMPOSITION discloses a composition used to build and sustain muscle mass. The complex is comprised of effective amounts of chromium salt and a magnesium glycyl glutaminate chelate as core ingredients. Optional ingredients include a magnesium amino acid chelate, an .alpha.-glutaric acid salt of ornithine, creatine (or a salt thereof) and a branched chain amino acid (leucine, isoleucine and/or valine).
Based upon what is known about the prior art, there is a need to provide a composition and method of making a compound that enables creatine and essential metals to be introduced to the body in such a manner so that more creatine than previously known in the art may be used by the body prior to undergoing cyclization. In other words, it would be desirable to provide a creatine chelate for oral consumption comprised in such a way that the creatine ligand is protected by the metal from undergoing cyclization in the acidic environment of the stomach, thus making the creatine more readily available to the body in a useful form. Further, it would be desirable to provide a creatine chelate so that the metal is made more bioavailable due to the presence of the creatine ligand.